| Project/Area Number |
15390102
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pathological medical chemistry
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| Research Institution | University of Fukui (2004)
福井医科大学 (2003) |
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Principal Investigator |
YOKOTA Yoshifumi University of Fukui, Department of Molecular Genetics, Professor, 医学部, 教授 (50222386)
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| Co-Investigator(Kenkyū-buntansha) |
KUROOKA Hisanori University of Fukui, Department of Molecular Genetics, Associate Professor, 医学部, 助教授 (00293879)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥15,400,000 (Direct Cost: ¥15,400,000)
Fiscal Year 2004: ¥5,900,000 (Direct Cost: ¥5,900,000)
Fiscal Year 2003: ¥9,500,000 (Direct Cost: ¥9,500,000)
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| Keywords | transcription factor / Id2 / cell differentiation / growth control / mammary epithelial cells / hydronephrosis / intracellular localization / 細胞内局在 / 乳腺 / B細胞 / サイクリン / 腸上皮間リンパ球 / 遺伝子欠損マウス |
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| Research Abstract |
1.Id2 KO mice develop intestinal tumors in the middle portion of the ileum, showing a variety of the pathological grade. Immunohistochemical analysis demonstrates no enhanced expression and no nuclear localization of β-catenin protein. Smad4, a transcription factor that mediates the TGF β signaling, was detected similar to the normal tissue, while Cdx2 was absent in the tumors. We are continuing to study the mechanisms underlying the tumor formation in Id2 KO mice.
2.Id2 protein was found to shuttle between the nucleus and the cytoplasm. The nuclear localization of the protein was dependent on the basic amino acid residues in the helix-loop-helix region. The nuclear export signal was found in the C-terminal region and the export was dependent on CRM1. In the steady state, the nuclear export of Id2 protein was stronger than the nuclear import.
3.Id2 KO mice share the lactation defect phenotype with C/EBP β KO mice. We identified Id2 as a direct target of with C/EBP β. In addition to in vitro analyses, we demonstrated that the induction of Id2 gene expression is not observed in the pregnant mammary gland of C/EBP β KO mice.
4.The population of CD8+ T cells in the spleen is reduced in Id2 KO mice. We found that the expression of cyclin-dependent kinase inhibitors such as p21 and p27 is elevated at the protein level in Id2-deficient CD8+ T cells.
5.Id2 KO mice are hyperactive due to the increased release of dopamine in the striatum. We failed to detect any significant difference in the numbers and localization of GABAergic neurons in pars reticulata of substantia nigra.
6.We found that Id2 KO mice develop congenital hydronephrosis due to the stenosis at the ureteropelvic junction. Observed characteristics of hydronephrosis in the mutant mice were similar to those in human cases. Furthermore, Id2 haploinsufficiency also caused the malformation. Therefore, it was strongly suggested that Id2 is a candidate gene responsible for the development of congenital hydronephrosis.
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